Safety Considerations in the Field of ADC

Antibody-Drug Conjugate (ADC) refers to a class of biotechnological drugs in which small molecule compounds (Payload) are conjugated to targeted antibodies (Antibody) or antibody fragments through a linker.

With the development of biopharmaceutical technology and consideration of drug safety, ADC drugs have also undergone four iterations.

Source: NextPharm® Database; Pharmcube Research and Analysis

Since the launch of the first ADC drug Mylotarg (which was withdrawn from the market in 2010 due to its serious side effects) in 2000, about 15 ADC drugs have been launched globally, of which 8 ADC drugs have been launched in China. Aidixi, an ADC drug independently developed by RemeGen, was approved for marketing in China on June 8, 2021, becoming the first domestically produced ADC drug approved for marketing.

Data source: Pharnex Consulting, "Global ADC Drug R&D Analysis"

Summary of Marketed Drugs

With the development of coupling technology, Chinese ADC enterprises have also made great efforts. Since the beginning of the 2021, with the licenses out of many Chinese companies, we have shown our strengthened R&D capabilities and market potential. Up to April 2024, many overseas transactions have taken place among Chinese companies.

Data source: Xueqiu

Chinese ADC enterprises' concentration on overseas expansion highlights their technological strength

The production process of ADC drugs can be divided into three steps: antibody production, small molecule drug intermediate production, and conjugation production. However, due to the involvement of chemical synthesis or fermentation in the production of small molecule compounds and related considerations of small molecule toxicity, most enterprises purchase them externally. This article does not cover the production process of small molecule compounds. In the biopharmaceutical industry, ADC can be divided into two process steps: antibody production and conjugation production.

Main Production Processes of ADC

Antibody Production: The process from upstream cell culture to downstream purification and subsequent formulation filling has become a relatively mature route. BioLink offers comprehensive solutions for antibody production, encompassing everything from cell recovery to upstream bioreactors for cell culture, as well as downstream purification equipment and various chromatography resins. These solutions can be tailored to provide equipment and resins suitable for both laboratory and production scales.

Conjugation Production: As the core process of ADC drugs, it requires an independent conjugation workshop for production. BioLink provides a comprehensive ADC solution to assist in the completion of plant design and construction, offering a full-process design plan for the ADC process.

During the conjugation reaction, it is necessary to consider process stability and safety, both of which can affect the final quality of ADC. Relevant safety considerations are required at different stages of development. The conjugation process involves the coupling of small molecule compounds with antibodies, which requires continuous stirring. In the stirring process, factors such as temperature, stirring time, pH value, reagent addition sequence during conjugation, and types of organic solvents need to be taken into account.

In response to the needs of the conjugation process, more and more enterprises are now choosing to use single-use solutions to replace traditional reactors, glass tanks, and other coupling methods. In terms of safety and energy efficiency, single-use solutions are significantly superior to traditional methods. They offer a closed environment, controllable temperature and pH control, and controllable stirring time. Additionally, they eliminate the need for CIP and SIP, traditional piping and tank systems, resulting in more efficient use of space and faster product changeovers. The elimination of corresponding cleaning validation work reduces the risk of cross-contamination and saves labor costs, validation costs, and maintenance costs.

Regarding the reproducibility and stable scaling-up of the process, single-use solutions are also the preferred options. Additionally, the use of single-use consumables takes into account the leachables/extractables of small molecule compounds, providing a safer and more reliable operating environment and scalability, which is also increasingly favored by users.

BioLink's single-use consumable validation, with a comprehensive validation system and validation projects, supports ADC production and meets relevant regulatory requirements.

Ultrafiltration plays an indispensable role as one of the most critical steps in the production of ADC drugs, serving different purposes at different stages. In the initial stage, it is used for solution replacement, and after coupling, it is used for the removal of small molecules and other impurities. Therefore, the selection of ultrafiltration is crucial in the ADC process.

BioLink's ultrafiltration system offers both single-use and reusable design options.

• Independent design, production, and quality system, flexibly adapted to customer needs

• Experienced ultrafiltration team with over 10 years of experience in related products

• Deep understanding of customer processes and DQ design, optimization of process parameters during material production

• Constant pressure/constant flow control for stable process parameter adjustment

• User-friendly interface with comprehensive computerized function qualification

• Mature validation documentation system to ensure reliable and compliant delivery processes and document logic

• Comprehensive after-sales system with efficient response speed and professional problem-solving capabilities

Design Solutions from Laboratory Scale to Commercial Scale

Depending on the different linkers and small molecule compounds selected during the coupling process, the choice of post-coupling processes also varies, presenting a diverse range of options. The use of ultrafiltration alone can achieve the desired results, or a combination of ultrafiltration and chromatography can be employed for purification. BioLink's MaXtar® S HC chromatography resin is stable in 15% DMSO solution for 200 hours, with high binding capacity, good pressure resistance, and simple operation. It is an ideal choice for purification of samples or purification systems containing DMSO solution, and for purification scheme after ADC coupling, improving product quality.

With professional technical support, a diverse product line, a high-standard quality management system, and comprehensive after-sales services, BioLink provides end-to-end solutions for the ADC field, catering to the full range of services from research and development to pilot testing to production. This enables rapid process integration and project transfer, providing customers with one-stop comprehensive solutions.